Medication-assisted Treatment of Opioid Addiction Reduces Incidence of Hep C

We already know that medication-assisted treatment of opioid addiction reduces the incidence of HIV. Indeed, people in active opioid addiction contract HIV six times more often than patients on medication-assisted treatment (Metzger et al, 1993). But previous studies haven’t shown clear reduction in the transmission of Hep C.

Until now.

This new study does show a reduction in the incidence of Hepatitis C in opioid addicts who enter medication assisted treatment.

This prospective observational study by Tsai et al of 552 opioid addicts was done in San Francisco from 2000 to 2013. All subjects tested negative for Hep C in order to enter the study, and all were under thirty years old. These addicts enrolled in various forms of treatment: opioid agonist detoxification with methadone or buprenorphine, opioid agonist maintenance treatment with either methadone or buprenorphine, or non-opioid agonist forms of treatment. Some of the group elected not to get any form of treatment. Follow up testing for Hep C was done quarterly.

One-hundred and seventy-one study subjects tested positive for Hep C as the study progressed, giving an incidence rate of 25% per 100 patient-years. However, the study subjects who entered opioid agonist maintenance treatment were significantly less likely to become Hep C positive as compared to the addicts who got non-opioid agonist treatment or opioid agonist detox treatment. Addicts who enrolled in opioid-agonist maintenance treatment had a 60% reduction in the incidence of Hep C compared to the other study groups, which was statistically significant.

The patients on opioid agonist maintenance therapy had an incidence of 8.6 new cases of Hep C during 100 person-years of the study, while the group of subjects who entered non- opioid agonist forms of treatment, which included 12-step recovery and other abstinence-based forms of treatment, had an incidence of 17.8 over 100 person-years. People who didn’t get any treatment had an incidence of 28.2 per 100 person-years, while opioid addicts who underwent detox only had the highest Hep C conversion rate of 41% per 100 person-years.

As alarming and confusing as this last bit was, the data didn’t reach statistical significance, so we shouldn’t draw any conclusions about that bit.

Other studies have suggested a lower rate of Hep C transmission in opioid addicts who enter medication-assisted treatment, but none showed this as definitely as did this study.

Several things stood out to me as I read the study – first, these were young people. The average age was 23, and the study purposely excluded addicts over age 30. Maybe younger age means less time of exposure to Hep C. Older populations may already have Hep C.

This study looked at opioid addicts who sound like they are sicker than addicts I admit to treatment. For example, a whopping 69% were homeless. Do the homeless re-use needles at a higher rate? I don’t know, but perhaps homeless people have fewer resources to get clean needles, and could be at higher risk for Hep C than the rural inhabitants I treat.

The most common drug of use was heroin, used by 60% of the study population. While heroin has just started to invade my rural area, most of my new patients use opioid pain pills. It seems possible that intravenous heroin users have progressed further into addiction than pain pill users.

Even if the subjects in this study aren’t exactly the same as patients I see, this is good evidence that medication-assisted treatment reduces the risk of Hep C. It’s not the best reason for entering MAT; not dying from an opioid overdose is the best reason. But still, reducing the risk of Hep C is a good thing.

Buprenorphine and the Liver

When buprenorphine was approved for office-based treatment of opioid addiction in the U.S, doctors worried about possible liver toxicity. We’d seen case reports of acute liver necrosis (death of liver tissue) in patients with Hepatitis C who injected buprenorphine illicitly. So was this damage due to the drug itself, from intravenous use of the sublingual product, or from buprenorphine interaction with Hepatitis C? Until we had more information, experts recommended checking liver function tests before starting buprenorphine and periodically during treatment to monitor for liver damage.

Fortunately, further studies show no liver damage in patients prescribed buprenorphine.

In 2012, Saxon et al followed over 700 patients on buprenorphine or methadone over 24 weeks, and checked their liver function tests periodically, looking for elevations that would indicate liver inflammation or damage. Neither patients on methadone or patients on buprenorphine had significant increase in their liver function test levels, leading the study’s authors to conclude that neither methadone or buprenorphine cause liver damage. Patients with Hep C who were in this study did have elevated liver enzymes, but did not get worse over the twenty-four months while taking either medication.

In the November/December, 2014, issue of American Journal on Addictions, a new study by Soyka et. al. found the same thing. This study looked at 181 patients on buprenorphine/naloxone and followed their liver enzymes for over a year. Thirty-six percent of these patients had Hepatitis C, a group who may be at increased risk for liver damage due to drugs and medications. Liver tests were done at baseline, then at 12 and 24 weeks, and at the end of the first year at 52 weeks. One to two percent of these patients showed mild elevation of liver tests but none had evidence of drug induced liver injury.

This latest study adds to the medical literature that shows buprenorphine isn’t damaging to the liver, even in patients with Hepatitis C, in patients who take the medication as intended. (For obvious reasons, no one would ever do a study asking patients to inject the sublingual form of buprenorphine, since the medication isn’t sterile and the study would put test subjects at risk for all sorts of complications.)

So do we still need to check liver function tests for patients on buprenorphine? Most of the published guidelines about how to prescribe buprenorphine in an office setting still recommend checking liver function tests, but this data from Saxon study and the Soyka study seem to indicate this isn’t a particularly helpful thing to do.

About half of my buprenorphine patients have no insurance. After reading these studies, I’ve decided not to ask my patients to get routine liver function tests. I still think they need screening for Hepatitis C. Some doctors would say liver function tests can suggest Hep C if they are elevated, but since it’s possible to have Hep C and normal liver function tests, I think their money would be better spent on Hep C testing. Patients who test positive would then need to get further testing, which would likely include liver function tests, as well as confirmatory testing for Hep C.

Let’s use new information to spend health care dollars wisely.

Hepatitis C: Now Curable

New medication combinations are giving Hep C cure rates of up to 75% with genotype 1, traditionally the toughest to treat. This is exciting news for the estimated 3.4 million people in the U.S. infected with the Hep C virus.

My last blog entry contained some general information about Hepatitis C viral infection, and the proper steps to take after a patient has screening tests that’s positive. If the second test, called a qualitative test, shows positive for the presence of the Hep C virus, what’s next?

In the past, many people didn’t get any further follow up testing done to see if they needed treatment, because cure rates were low, medication expensive, and the medication makes many people ill. Only about15% of people with hepatitis C go on to have cirrhosis, but the sheer number of people infected in the U.S. means there will be many people diagnosed with cirrhosis.

Now that much higher cure rates are being achieved, patients with Hep C infection need to get themselves to a liver specialist. Since cure rates are much improved, if treatment is needed, it may be time to get on with it.

To see if treatment is needed, most specialists still want to do a liver biopsy to determine the amount of damage, if any, that the Hep C virus is doing to the patients. The liver biopsy is relatively simple, with a complication rate of less than half of one percent even for patients with liver damage.

This liver tissue sample is studied under the microscope and given a Metavir score. This score, ranging from 0 to 4, tells us how much damage there has been to the liver.  A “0” score shows no damage at all, a very good thing. A score of 1 means there’s a small amount of fibrosis, or scarring, and so on until the score of 4 which means cirrhosis with much scarring is seen.

Most hepatologists (liver specialists) have not been treating patients with a Metavir score of 0 through 2, and most do recommend treatment for patients with a score of 3 or 4, since these higher scores mean there is ongoing liver damage. If the patient is already in end-stage liver disease, he may be unable to tolerate the treatment. In such a case, the hepatologist may not recommend treatment even for a patient with a Metavir score of 4.

In the past, treatment consisted of interferon and ribavirin, two agents that worked on the patient’s immune system. This treatment gave response rates of around 40 to 50%, at least with Hep C genotype 1. Genotypes 2 and 3, seen less commonly in the U.S., are easier to treat and had higher response rates.

Now there are two directly-acting agents that can be used with interferon and ribavirin: boceprevir and telaprevir. They are both protease inhibitors, and act directly on the virus, instead of on the patient’s immune system. This triple therapy is, at present, only indicated for the treatment of patients with genotype 1.

In a recent Phase II trial, telaprevir, combined with ribavirin and interferon and taken for 24 weeks, gave sustained viral response rates of 75%. This was in the group of patients who had never been treated. In patients who had been previously been treated for Hep C with just interferon and ribavirin, an new course of treatment with all three medications resulted in sustained responses in 88% of patients.

This is big news. These results are the best seen to date in the treatment of Hep C.

Some specialists still argue whether a sustained response means the same thing as a cure, but we now have long-term studies on patients who respond to interferon-based treatments. A recent study of 344 patients showed that when studied more than three years after successful treatment, the virus remained undetectable in 98.3% of these patients. Even more exciting, regression of cirrhosis was seen in 64% of these patients. This means that not only did these patients still have no detectable Hep C virus, the liver scarring improved.

This combination of three medications that work in different ways probably works better because the Hep C virus tends to change and mutate in small ways, and can become resistant if only one type of anti-viral medication is used.

Now for the bad news: both of these medications do have significant side effects. Treatment with just interferon and ribavirin is hard enough, but addition of either of these new medications makes treatment even more difficult. For example, telaprevir must be taken with large amounts of fat for better absorption, and can cause rectal pain and burning if it’s not well-absorbed. Many patients have lowered counts of red and white blood cells as well as low platelets. Some people can get a potentially fatal rash.

Even in view of the added difficulty, the markedly improved response rates, which appear to be cure rates, may make it worthwhile to consider treatment. In the future, specialists predict drug regimens that don’t have to include interferon. Soon there may be specific direct-acting agents for all of the genotypes of Hep C, with cure rates predicted to be as high as 90%. Courses of medications are expected to become ever shorter with fewer side effects.

Because we have better treatments, and because the Center for Disease Control and Prevention is recommended expanded testing for Hep C to include all baby boomers, it’s likely we’ll uncover many more cases of active Hep C.

My only worry is that diagnosing patients won’t help anyone unless it’s linked to coverage for further testing and treatment.

Patients at my clinics who screen positive for Hep C can’t even afford the confirmatory testing that they need to see if they have an active infection, if they have no insurance. Their local Health Department isn’t set up to do this kind of testing. Local doctors can’t afford to give this free care. There are some low-cost community clinics, but they don’t seem to be set up to afford the expensive testing needed for these patients. And what if they do have the virus? How can they pay to see the liver specialist and get the biopsy? Who pays for the very expensive treatment if they have no insurance?

When I worked at an opioid treatment program near a teaching hospital, it was possible to get an appointment for that patient in the resident physicians’ general medicine clinic, where they could get further testing and be referred for specialty care if needed. It’s a much bigger challenge for patients who live where there are few low-cost options for medical for the uninsured.

Because of the exciting new developments in the treatment of Hep C, there are many ongoing clinical trials. For patients with no insurance, enrolling in a clinical trial may be a way to get some medication for free, though you probably wouldn’t be able to pick which treatment regimen you get.

If you have Hep C, and are fortunate enough to afford it, it’s definitely worth consulting – or re-consulting – with a liver specialist to see what your best options are.

Though the new hepatitis medications do have some serious drug interactions, they aren’t a problem with either methadone or buprenorphine.

Hepatitis C: What’s New?

A fair number of my patients screen positive for the Hepatitis C virus. Obviously, they want to know what a positive screening test means, and what they should do next. Since a positive screen doesn’t necessarily mean an infection with Hep C, I’d like to explain more about this test, about the virus, and what’s new in the treatment of Hep C.

Hepatitis C is a virus that mainly affects the liver, as its name implies. There are other viruses that affect the liver, creatively named Hepatitis A, Hepatitis B, and so on. But Hepatitis C is the biggie, with an estimated 3.4 million people in the U.S. with the infection. In fact, it’s the most common chronic blood-borne viral infection in the U.S.  Around the world, 180 million people are estimated to be infected with Hep C.

Anyone with a history of intravenous drug use should be screened for hepatitis C. In the U.S., this is the most common way of contracting the virus. Even if you didn’t share needles, if you shared cookers, water, spoons or other material, you may have contracted the virus. Even people who shared straws to snort drugs appear to be at risk, and should be tested.

It’s a blood-borne illness, so it can also be transmitted through tattoos with unclean needles, re-used medical supplies, and blood transfusion with tainted blood. However, risks of infection through transfusion in the U.S. are very low since testing for the virus became available in 1992.

Most people who have hepatitis C got it from another person’s blood, but it can be transmitted through sex. In monogamous couples with one infected partner, the virus is transmitted to the uninfected partner in only about 1 – 5% of cases. However, multiple sexual partners and high risk sexual activities result in higher transmission rates. You can’t transmit Hep C by hugging, kissing, sharing eating utensils or ordinary household contact, though a person with Hep C shouldn’t share razors or toothbrushes.

In May of this year, the Centers for Disease Control and Prevention recommended one-time testing for Hepatitis C in all baby boomers, meaning people born between 1945 and 1965. About one in thirty baby boomers have hepatitis C, according to the CDC. Because newer treatments can cure chronic Hep C infection, the CDC hopes to save an estimated 120,000 lives by uncovering infections in people who don’t know they’re infected.

The screening test for Hep C is relatively inexpensive, and screens only for antibodies to the Hepatitis C virus. If you screen positive with this test, it means you have been exposed to the Hep C virus. It does not tell us if you have chronic Hepatitis C infection. Up to 20% of people who contract Hepatitis C infections are able to clear the virus on their own, and will not have chronic infection. However, they will remain positive on this screening test, because they will carry antibodies against the virus for the rest of their lives. Patients diagnosed, treated, and cured of Hep C infection will also remain positive for Hep C on this antibody screening test, so it’s not helpful to screen these patients again. In fact, it may be confusing if the provider doesn’t understand what this antibody test means, and explain it adequately to patients.

There are six specific types, called genotypes, of Hepatitis C. Even if you clear the infection to one genotype, you can be re-infected with another genotype of hepatitis C. If you have active Hep C and continue to share needles, it’s possible to become infected with more than one subtype.

There’s no vaccine available for Hep C like there is for Hep A and B. Much like HIV, the Hep C virus undergoes frequent changes, so it’s like making a vaccine against a moving target.

If you test positive on screening for Hep C, you need to have further testing to see if you have Hepatitis C infection. The next step is a qualitative test for hepatitis C. At around $100 at the cheapest, it’s difficult for patients without insurance to afford the proper testing.  If this qualitative test is positive, you should then see a specialist to see if you need a liver biopsy. Most specialists base the decision to treat on a liver biopsy. There are other tests, but biopsy is still the gold standard.

If treatment is contemplated, it will be necessary to have genotype testing, to find out what specific type of Hep C you have. Treatments are different for different subtypes. Two new medications are used in the treatment of type 1, the most frequent type in the U.S., and give cure rates up to 75%. On the other hand, genotypes 2 and 3 are more easily treated and don’t require treatment to be as long as type 1. Quantitative Hep C testing, called viral counts, isn’t needed unless treatment is going to be done, when it is used to follow the response to treatment. Outside of that, the viral count provides little information.

Liver function tests, called LFT’s, are relatively cheap, and are often done at the same time as the first Hep C screening test. If they are elevated, it usually means there’s inflammation in the liver. Many things can cause an increase in LFTs. Alcohol is the most common cause, but all viral hepatitis infections can cause elevations too. However, it’s possible to have normal LFT’s and still have active Hepatitis C. We can’t assume you don’t have Hep C infection even if your LFT’s are normal.

If you have Hepatitis C, you should NEVER drink alcohol. Even patients infected with Hep C but with no problems on liver biopsy will go downhill fast if they drink alcohol. The dangers of alcohol in patients with Hep C cannot be overstated. Don’t. Drink. Ever. Not even a cold beer after mowing the lawn.

In my next blog post, I’ll talk about the exciting new treatment developments.

Hepatitis C in Opioid Addicts

Hepatitis C infection is common in people who have abused or been addicted to drugs. Of course, sharing needles is the biggest risk for contracting Hepatitis C. Some studies have found that about 90% of methadone maintenance patients who have used intravenously screen positive for the antibodies to Hepatitis C, and over 60% had active infection with the virus.(1) A Canadian study showed similar rates; 90% of intravenous drug users screened positive for Hepatitis C in that country, too. (2) It’s not only people who have shared needles to inject drugs. There’s some evidence to show Hepatitis C can be transmitted by people sharing paraphernalia to snort drugs. (3) For this reason, it would seem obvious that patients who are addicted to opioids and entering treatment need to be checked for Hepatitis C.

Worldwide, there are an estimated 170 million people infected with Hepatitis C, and more than 3 million in the U.S. Hepatitis C is the primary reason for liver transplantation in this country. About 85% of people in the U.S. with Hepatitis C either have a history of intravenous drug use, or had blood transfusions prior to 1992, when the screening test specific for Hepatitis C was released.

It’s easy to test for the virus.

It requires only a blood test to screen for Hepatitis C. The initial test looks for antibodies against the Hepatitis C virus. If this test is positive, it means the person has probably been exposed to the virus, but doesn’t tell if the virus is active. Positive screening tests only mean that further testing is necessary.

Follow up tests for the actual Hepatitis C virus, called antigen tests, are needed next. If the virus is present, viral counts are done, and the virus is sub typed. Since these subtypes, called genotypes, of the Hepatitis C virus respond differently to treatment, the information indicates the likelihood of response to treatment. Even if the Hep C virus is present in high amounts, it doesn’t necessarily mean the liver is damaged. The only way to know for sure is with a liver biopsy.

It causes significant health issues.

Not everyone with Hepatitis C has a chronic infection, but of those that do, around 20% progress to cirrhosis, and around 4% develop hepatocellular carcinoma. Therefore, Hepatitis C can cause significant health issues, to put it mildly. It can cause a whole host of other illnesses, too: kidney diseases and various autoimmune diseases.

It’s treatable.

Not all cases of chronic Hep C need treatment. Some patients are fortunate to carry the virus without ever having problems from it. But other patients need treatment. As stated above, some subtypes of Hepatitis C are easier to treat than others, so the duration of treatment is longer for patients with harder-to-treat genotypes. Of patients with Genotype 1, around half have successful outcomes with treatment consisting of interferon and ribavirin. With Genotype 2, rates are even better, with around 80% of patients having successful results with treatment. The treatment can be difficult for many patients, and often causes depression, marked fatigue, and other unpleasant symptoms. Research continues on Hepatitis C, and hopefully there will soon be better treatments available.

People with known infections with Hepatitis C can take precautions.

Hepatitis C is commonly transmitted by shared needles and re-used medical supplies, and by tattoos and body piercing, if performed with reused equipment.  It’s spread by sexual contact surprisingly infrequently, but condoms are still recommended if one partner is positive for Hep C and the other one is negative. It’s probably easier to transmit sexually if there are open sores on the genitals, or trauma to delicate tissues that causes a break in the skin. It can be transmitted by an infected mother to her fetus, but only in about 6% of such pregnancies. Since Hep C is carried in the blood, there’s a remote chance of spreading it by sharing razors and even toothbrushes.

People with Hepatitis C infection need to take some health precautions. They need to be immunized against Hepatitis A and B, if they haven’t already received these. Presently there isn’t a vaccine to prevent Hepatitis C.

This information shows how important it is to screen for Hepatitis C. However, at least in this area of the country, it’s not common to screen patients for Hepatitis C when they enter treatment at opioid treatment centers. This is due to the cost of the testing, and lack of available follow up services. At the opioid treatment program where I presently work, Hepatitis B and C testing is encouraged, but the patients have to pay for the tests. The treatment center only charges what they have to pay the lab; there’s no mark up, and no profit in testing for the treatment center. Even then, fewer than half of the entering patients agree to this screening. At present, it costs around $25 for Hepatitis C initial screening. Fortunately, Hepatitis B screening is much cheaper.

When I have to inform patients about a positive Hepatitis C screen, what’s the next step? Most of the patients I’ve seen at this clinic who screen positive for the hepatitis C antibody don’t have insurance to help them get further testing. They don’t qualify for Medicaid, and they certainly can’t pay for treatment, if it’s needed. Sometimes I feel like I give these patients another burden to worry about, and I wonder if I’m doing more harm than good.

At an opioid treatment program where I worked in the past, I was able to form a relationship with a nearby university hospital. This town had a medical school and residency program, and people without insurance could be seen by the doctors in training. I could make appointments for patients who screened positive for hep C and further testing. The wait was about four months, but if the patient kept his appointment (often quite a challenge), he could then be referred to liver specialists associated with the medical school, if it appeared that a liver biopsy would be needed. Once these patients are established at this program, they can be entered into a research study, if one is available and they meet entrance criteria.

At the opioid treatment program where I now work, it’s harder to find places to refer patients with no money and no insurance. Most often, they go without care. At the very least, they can go to the local county health department and get needed Hepatitis A and B vaccinations and they know the sort of precautions they should take to prevent transmission, until they can get further testing. I’m going to keep looking for places to send patients without insurance, but it’s a problem. In this area, it’s hard for them to even find a primary care doctor.

1. McCarthy JJ, Flynn N, “Hepatitis C in methadone maintenance patients: Prevalence and public policy implications,” Journal of Addictive Diseases, 2001;20:19-31.
2. Patrick DM, Buxton JA, Bignam M, et. al., “Public Health and Hepatitis C,” Canadian Journal of Public Health, 2000;91(S1):S18-S23.
3. Aaron, S, McMahon, JM, Milano, D, et. al., “Intranasal transmission of hepatitis C virus: virological and clinical evidence.” Clinical Infectious Diseases, 10/1/08,47(7):931-934.